1

AGIOS 2025 VISIONMarch 2020 Corporate Presentation

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Forward Looking Statements

This presentation and various remarks we make during this presentation contain forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding Agios’ plans, strategies and expectations for its and its collaborator’s preclinical, clinical and commercial advancement of itsdrug development programs including TIBSOVO® (ivosidenib), IDHIFA® (enasidenib), mitapivat, vorasidenib, AG-270 and AG-636; the potential benefits of Agios' product candidates; Agios’s strategic vision and goals for 2025; its key milestones for 2020; its estimates regarding its balance of cash, cash equivalents and marketable securities for the year ended December 31,2019; its plans regarding future data presentations; its financial guidance regarding the period in which it will have capital available to fund its operations; and the potential benefit of its strategic plans and focus. The words “anticipate,” “expect,” “hope,” “milestone,” “plan,” “potential,” “possible,” “strategy,” “will,” “vision,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Such statements are subject to numerous important factors, risks and uncertainties that may cause actual events or results to differ materially fromAgios' current expectations and beliefs. For example, there can be no guarantee that any product candidate Agios or its collaborators is developing will successfully commence or complete necessary preclinical and clinical development phases, or that development of any of Agios' product candidates will successfully continue. There can be no guarantee that any positive developments in Agios' business will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this presentation and various remarks we make during this presentation could also be affected by risks and uncertainties relating to a number of other important factors, including: Agios' results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. FDA, the EMA or other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies; Agios' ability to obtain and maintain requisite regulatory approvals and to enroll patients in its planned clinical trials; unplanned cash requirements and expenditures; competitive factors; Agios' ability to obtain, maintain and enforce patent and other intellectual property protection for any product candidates it is developing; Agios' ability to maintain key collaborations; and general economic and market conditions. These and other risks are described in greater detail under the caption "Risk Factors" included in Agios’ public filings with the Securities and Exchange Commission. Any forward-looking statements contained in this presentation and various remarks we make during this presentation speak only as of the date hereof, and Agios expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise, except as required by law.

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We are driven by our

sense of urgency to

help patients.

LEARN MORE AT KNOWPKDEFICIENCY.COM

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Our Strategy is Clear

For more than a decade, our mission has been to create differentiated, small molecule medicines for patients in three focus areas – malignant hematology, solid

tumors and rare genetic diseases – based on our unique expertise in cellular metabolism and adjacent areas of biology

METABOLISM

SOLIDTUMORS

2

RARE GENETIC

DISEASES

3

MALIGNANT HEMATOLOGY

1

5

Our People and Culture Fuel Incredible Productivity, Strategic Focus and Continuity from Early Research to Market

“Other Side OfPossible” Culture

Patient-centricApproach

Creative Clinical Development

ProductiveResearch Engine

4 ADDITIONAL MOLECULES IN CLINICAL DEVELOPMENT2 MEDICINES

APPROVED +~550

HIGH CALIBER EMPLOYEES WITH 1 VISION

10 YEARS

7INVESTIGATIONAL NEW

DRUG CANDIDATES

70+ PEER-REVIEWED PUBLICATIONS

15+ RESEARCH PROGRAMS

1,500+ PATIENTS TREATED IN OUR

CLINICAL TRIALS

6

Agios 2025 Vision: Focused Innovation. Ambitious Development. Transformative Treatments for Patients Across Three Focus Areas.

NOW

CASH FLOWPOSITIVE

2025

FINANCIAL$105-115M

EXPECTED U.S. TIBSOVO®

2020 REVENUE

4MEDICINES

COMMERCIAL 2 MEDICINES

8+ INDICATIONS

LABELEXPANSION

2INDICATIONS

6+ MOLECULES IN THE CLINIC

PRODUCTIVE DISCOVERY

ENGINE4

MOLECULES IN THE CLINIC

77

Multiple Potential Near- and Long-term Value Drivers Across All Focus Areas

2020 2021 2022 2023 2024 2025

Approval Make go/no-go decision

TIBSOVO® R/R AML EU

TIBSOVO® IC-ineligible 1L AML (AGILE Phase 3)

TIBSOVO® IC-eligible 1L AML (HOVON Phase 3)

TIBSOVO® R/R MDS (Phase 1 expansion)

AG-636 Advanced Lymphoma

HEM

ATO

LOG

IC

MA

LIG

NA

NC

IES

TIBSOVO® Cholangiocarcinoma (ClarIDHy Phase 3)

Vorasidenib Low-grade Glioma (INDIGO Phase 3)

AG-270 Non-small Cell Lung Cancer

AG-270 Pancreatic Cancer

SOLI

DTU

MO

RS

Mitapivat TD Adult PK Deficiency (ACTIVATE-T)

Mitapivat Pediatric PK Deficiency

Mitapivat Thalassemia

Mitapivat Sickle Cell Disease

Mitapivat NTD Adult PK Deficiency (ACTIVATE)

RA

RE

GEN

ETIC

D

ISEA

SES

8

Highly Productive Research Engine with Optionality Across Focus Areas Program Target Discovery Target Validation Drug Discovery Drug Candidate

Solid Tumor

Non-Metabolic TargetMetabolic Target Metabolic and Non-Metabolic Targets Bristol-Myers Squibb Collaboration

Malignant Hematology

Rare Genetic Diseases

MAT2A Follow-Ons

Macrophage I-O Target

Tumor I-O Target

Genetically Defined Solid Tumor Target

Metabolic I-O Exploratory Programs

Other Exploratory Programs

MAT2A Follow-Ons

Macrophage I-O Target

Tumor I-O Target

Genetically Defined Heme Target

Metabolic I-O Exploratory Programs

Other Exploratory Programs

AG-946 (Pyruvate Kinase Activator Follow-On)

Phenylketonuria (PKU)

Erythroid Porphyria

Friedreich’s Ataxia

Other Exploratory Programs

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2

3

1 Malignant Hematology

Solid Tumors

Rare Genetic Diseases

CREATING MEDICINES IN THREE FOCUS AREAS

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1 Malignant Hematology

CREATING MEDICINES IN THREE FOCUS AREAS

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Significant Growth Potential in Malignant Hematology

IDH1 Mutant Acute Myeloid Leukemia (AML)

IDH1 Mutant Myelodysplastic Syndrome (MDS)

Mantle Cell and Diffuse Large B Cell Lymphoma

TIBSOVO®

R/R AML U.S. Approval; MAA Under Review

1L Monotherapy U.S. Approval

1L HMA Combo Phase 3

1L 7+3 Combo Phase 3

TIBSOVO® AG-636

R/R MDS Phase 1 Expansion R/R Lymphoma Phase 1

~4KPATIENTS IN

U.S. & EU

<1KPATIENTS IN

U.S.

~55KPATIENTS IN

U.S. & EU

Source: Agios estimates, market research, SEER, MDS Foundation, Datamonitor

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Successful TIBSOVO® Launch in R/R and Frontline AML Result of Focused Commercial Effort

$9

$14

$17$20

Q1 2019 Q2 2019 Q3 2019 Q4 2019

TIBSOVO® Revenue

$105 – 115MU.S. Net Sales Guidance for 2020

$60M Full Year 2019 Product Revenue

~515Unique Prescribers as of Q4 2019

>1,000Patients Treated Since Launch

Source: Agios estimates

(in millions)

Core commercial capabilities support two additional TIBSOVO® indications by YE 2022

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AGILE Phase 3 Aza Combo Enrolling

Phase 1 combo data:61% CR 70% CR+CRh82% 12-month OS

Phase 1 combo data:79% CR in de novo AML

53% CR in secondary AML79% 12-month OS

HOVON Phase 3 7+3 Combo

Enrolling

TIBSOVO®

Monotherapy Approved

HOVON 7+3 Phase 3 Enrolling

TIBSOVO®

Approved in U.S. MAA Under Review

TIBSOVO®

Monotherapy Approved

AGILE Phase 3 Aza Combo Enrolling

xs

~50%Eligible for

intensive therapy

~25%Currently untreated

~25%Ineligible for

intensive therapy

Advancing Toward Largest Opportunity for mIDH1 AML: Intensive and Non-Intensive Therapy Combinations

50K AML Patients Diagnosed Per Year in U.S. and EU6-10% with an IDH1 Mutation

Sources: SEER. Cancer Stat Facts: AML 2015 and Epiphany EPIC oncology numbers; American Cancer Society. AML 2017.

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2 Solid TumorsCREATING MEDICINES IN

THREE FOCUS AREAS

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Four Distinct Solid Tumor Opportunities Across Three Clinical Molecules

TIBSOVO® Vorasidenib

IDH1 Mutant Cholangiocarcinoma

IDH Mutant Low Grade Glioma

MTAP-Deleted Non-Small Cell Lung Cancer

MTAP-Deleted Pancreatic Cancer

~2-3KPATIENTS IN

U.S. & EU

~9K PATIENTS IN

U.S. & EU

~9K PATIENTS

IN U.S.

~10K PATIENTS

IN U.S.

R/R Cholangio sNDA 2020 Low-grade Glioma Phase 3

AG-270

2nd Line NSCLC Phase 1 Combo

AG-270

1st or 2nd Line Pancreatic Cancer

Phase 1 Combo

Source: Agios estimates, market research

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POSITIVE CLARIDHY RESULTS

FEWTREATMENT

OPTIONS

Sources: CDC National Program of Cancer Registries (NPCR); Epiphany Partners Epic Oncology; Decision Resources; Market Research; Borger DR et al. Oncologist 2012;17:72-9.; Kipp BR et al. Hum Pathol 2012;43:1552-8.; Goyal L et al. Oncologist 2015;20:1019-27; data from ESMO 2019

Established Utility of IDH Inhibition in Solid Tumors with Positive ClarIDHy Phase 3 Study of TIBSOVO® in Second-line or Later Cholangiocarcinoma

~9%FIVE-YEAR OVERALL SURVIVAL

RATE

0APPROVED THERAPIESFOR mIDH1 PATIENTS

63%REDUCTION IN

RISK OF DISEASE PROGRESSION OR

DEATH FOR PATIENTS

TREATED W/ TIBSOVO®

PFS

prob

abili

ty

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

HR=0.37 (95% CI 0.25, 0.54) P<0.001

Censored+ PlaceboIvosidenib

Phase 3 ClarIDHy Study Achieved Primary Endpoint, Demonstrating Statistically Significant Improvement in PFS

Mature OS from ClarIDHy Phase 3 expected mid-2020; sNDA planned by YE

LOW SURVIVAL

RATES

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Global Phase 3 INDIGO Study of Vorasidenib in IDH Mutant Low-Grade Glioma Open and Enrolling

1:1 double-blind randomization

(n=366)

*centrally-confirmed progressive disease will permit unblinding and crossover

Vorasidenib50 mg QD orally

Continuous 28-day cycles(n=183)

Matched placebo*(n=183)

Stratified by 1p19q status and baseline tumor size

BIRC = blinded independent review committee, ORR = overall response rate, OS = overall survival, QOL = quality of life, WHO = World Health Organization; Source: Data presented at SNO 2019

EndpointsPrimary: Progression free survival (by BIRC)Secondary/Exploratory: Tumor volume, safety, ORR, OS, QOL, seizures, neuro-cognitive function, time to next intervention

ENCOURAGINGPHASE 1 DATA

IMPRESSIVE PRELIMINARY

EFFICACYDATA

>90%2-HG

SUPPRESSION IN RESECTED

mIDH1 GLIOMAS ACROSS ALL

DOSES TESTED

33% ORRIN THE

VORASIDENIBARM OF THE

PERIOPERATIVE STUDY

22 mo.MEDIAN

TREATMENT DURATION IN VORASIDENIB

PHASE 1

SIGNIFICANT 2-HG

SUPPRESSION

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AG-270, MAT2A Inhibitor, Preclinical Data Supports Combination with Taxanes; Two Phase 1 Combination Arms Enrolling Patients

4 of 8 animals were tumor free at last dose and remained

tumor free until the arm was terminated on Day 141

PHASE 1 COMBINATION ARMS INITIATED

AG-270 + docetaxel in MTAP-deleted NSCLC

(2nd line)N = up to 40

AG-270 + nab-paclitaxeland gemcitabine in

MTAP-deleted pancreaticductal adenocarcinoma

(1st or 2nd line)N = up to 45

Modest near-term investment to enable pivotal strategy decision by YE2022

Source: Data presented at AACR-NCI-EORTC 2019

AG-270 + docetaxel induces 91% tumor growth

inhibition

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3 Rare Genetic Diseases

CREATING MEDICINES IN THREE FOCUS AREAS

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PKR Activation Represents Unique Mechanism of Action with Potential to Address Broad Range of Hemolytic Anemias

Normal Red Cell

PEP

Pyruvate

wtPKR

Cellular demand:

ATP production meets demand

Pyruvate Kinase Deficiency

PEP

Pyruvate

mPKR

Proof-of-concept achieved Adult PK deficiency approval expected in 2021 Pediatric PK deficiency pivotal strategy to be

finalized in 2020

Cellular demand:

Inadequate production: ATP deficiency

Other Hemolytic Anemias

PEP

Pyruvate

wtPKR

Thalassemia proof-of-conceptachieved

NIH sponsored trial in sickle cell disease ongoing

Increased demand: ATP deficiency

Cellular demand:

2121

Mitapivat has Potential to be First Disease-modifying Therapy for Patientswith PK Deficiency

Improvements in Hemoglobin and Other Hemolysis Markers Maintained for More Than 3 Years in Responding Patients from

DRIVE PK Extension

Chronic daily dosing with mitapivat for a median of 3 years and up to 42 months was well tolerated

HIGH RISKOF IRON

OVERLOAD

SUPPORTIVECARE ONLY

HIGHER LIFETIME RATES OF

PULMONARY HYPERTENSION, OSTEOPOROSIS,

AND LIVER CIRRHOSIS

0APPROVED THERAPIES

38%OF PATIENTS NOT

RECEIVING REGULAR

TRANSFUSIONS EXPERIENCE IRON

OVERLOAD

Source: Data presented at ASH 2019; van Beers EJ, et al. Haematologica. 2019;104(2):e51-e53.

COMPLICATIONS &COMORBIDITIES

REGARDLESS OFTRANSFUSION

STATUS

Topline data from ACTIVATE and ACTIVATE-T expected by YE 2020

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Clinical Proof-of-concept for Mitapivat Established in Non-transfusion-dependent Thalassemia

In responding patients, the mean hemoglobin increase from baseline was 1.76 g/dL (range, 0.9 – 3.3 g/dL)

Majority of adverse events were Grade 1 or 2 and consistent with previously published Phase 2 data for mitapivat in patients withPK deficiency

Updated Phase 2 thalassemia data to be submitted for presentationat EHA and pivotal strategy to be finalized by YE 2020

7 of 8 efficacy evaluable patients achieved a hemoglobin increaseof ≥1.0 g/dL from baseline in at least one assessment (weeks 4 – 12)

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Therapeutic Hypothesis for Wildtype PKR Activation in Sickle Cell Disease: 2,3-DPG and ATP Modulation Improves Anemia and Reduces Sickling

ATP-dependent regulation of

ion concentration and cellular shape

RBC dehydration3

↑ HbS concentration and polymerization3

↓ Deformability4

Water and ion loss3

↓ ATP in SCD1,2

Ca2+ entry3

Water and ion homeostasis

ATP, adenosine triphosphate; HbS, sickle cell hemoglobin; RBC, red blood cell; SCD, sickle cell disease.1. Palek J, Liu SC. J Supramol Struct. 1979;10(1):79-96. 2. Glader BE, et al. Br J Haematol. 1978;40(4):527-32.3. Bogdanova A, et al. Int J Mol Sci. 2013;14(5):9848-72. 4. Park Y, et al. Proc Natl Acad Sci USA. 2010;107(4):1289-94.

2,3-DPG Shifts the Oxygen Saturation Curve

Low DPG

High DPG

Expect to establish proof-of-concept for PKR activation in sickle cell disease by mid-2020

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PKR Activation Has Potential Broad Utility Across Hemolytic Anemias

Pyruvate Kinase Deficiency

~3-8KPATIENTS IN

U.S. & EU

β- and α-Thalassemia

~18-23K

PATIENTS IN U.S. & EU

Sickle Cell Disease

~120-135K

PATIENTS IN U.S. & EU

NTD β- and α-Thalassemia Phase 2

Thalassemia Pivotal Plan by YE

NTD Adult PKD Phase 3 Enrollment Closed

TD Adult PKD Phase 3 Enrollment Closed

Pediatric PKD Pivotal Plan by YE

Adult SCD NIH CRADA

Source: Agios estimates, market research

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2

3

1 Malignant Hematology

Solid Tumors

Rare Genetic Diseases

CREATING MEDICINES IN THREE FOCUS AREAS

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HEMATOLOGIC MALIGNANCIES

SOLID TUMORS

RARE GENETIC DISEASES

RESEARCH

Agios 2020 Key Milestones

Achieve full-year U.S. revenue for TIBSOVO® $105-115M Receive CHMP opinion for TIBSOVO® in mIDH1 relapsed/refractory AML Complete enrollment in AGILE Phase 3 trial of TIBSOVO® + azacitidine in frontline mIDH1 AML Complete enrollment in MDS arm of TIBSOVO® Phase 1

File sNDA for TIBSOVO® in mIDH1 previously treated cholangiocarcinoma

Topline data in PK deficiency from ACTIVATE and ACTIVATE-T Present data from mitapivat Phase 2 thalassemia study and finalize pivotal trial strategy in thalassemia Achieve proof-of-concept for mitapivat in sickle cell disease Initiate first-in-human study for next generation PKR activator, AG-946

Achieve at least 1 new development candidate

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AGIOS 2025 VISION:Focused Innovation. Ambitious Development.

Transformative Treatments for Patients Across Three Focus Areas.

4MEDICINES

8+ INDICATIONS

6+ MOLECULES

IN THE CLINIC

$CASH FLOW

POSITIVE